Method and apparatus for neural stimulation with respiratory feedback

ABSTRACT

A neural stimulation system controls the delivery of neural stimulation using a respiratory signal as a therapy feedback input. The respiratory signal is used to increase the effectiveness of the neural stimulation, such as vagal nerve stimulation, while decreasing potentially adverse side effects in respiratory functions. In one embodiment, the neural stimulation system synchronizes the delivery of the neural stimulation pulses to the respiratory cycles using a respiratory fiducial point in the respiratory signal and a delay interval. In another embodiment, the neural stimulation system detects a respiratory disorder and, in response, adjusts the delivery of the neural stimulation pulses and/or delivers a respiratory therapy treating the detected respiratory disorder.

CLAIM OF PRIORITY

This application is a divisional of and claims the benefit of priorityunder 35 U.S.C. §120 to U.S. patent application Ser. No. 11/468,595,entitled “METHOD AND APPARATUS FOR NEURAL STIMULATION WITH RESPIRATORYFEEDBACK,” filed on Aug. 30, 2006, now issued as U.S. Pat. No.8,121,692, which is incorporated by reference herein in its entirety.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is related to commonly assigned U.S. patent applicationSer. No. 11/467,264, entitled “SYSTEM FOR ABATING NEURAL STIMULATIONSIDE EFFECTS,” filed on Aug. 25, 2006, published as US 20080051839, nowU.S. Pat. No. 8,103,341, and U.S. patent application Ser. No.11/468,603, entitled “METHOD AND APPARATUS FOR CONTROLLING NEURALSTIMULATION DURING DISORDERED BREATHING” filed on Aug. 30, 2006,published as US 20080058873, now U.S. Pat. No. 8,050,765, which arehereby incorporated by reference in their entirety.

TECHNICAL FIELD

This document relates generally to neural stimulation and particularlyto a system for controlling neural stimulation using a respiratorysignal.

BACKGROUND

Electrical stimulation of the autonomic nervous system has been appliedto modulate various physiologic functions. One example is the modulationof cardiac functions and hemodynamic performance using neuralstimulation. The myocardium is innervated with sympathetic andparasympathetic nerves. Activities in these nerves, includingartificially applied electrical stimuli, modulate the heart rate andcontractility (strength of the myocardial contractions). Electricalstimulation applied to the parasympathetic nerves, such as the cardiacbranch of the vagus nerve, is known to decrease the heart rate and thecontractility, lengthen the systolic phase of a cardiac cycle, andshorten the diastolic phase of the cardiac cycle. Electrical stimulationapplied to the sympathetic nerves is known to have essentially theopposite effects.

The ability of the electrical stimulation of the autonomic nerves inmodulating the heart rate and contractility is utilized to treatabnormal cardiac conditions, such as to improve hemodynamic performancefor heart failure patients and to control myocardial remodeling andprevent arrhythmias following myocardial infarction. However, theautonomic nervous system regulates functions of many organs of the body.Neural stimulation pulses delivered to the autonomic nervous system totreat a cardiac disorder may unintentionally modulate various otherphysiologic functions. Therefore, there is a need to prevent or controlunintended, potentially adverse effects when neural stimulation isapplied to the autonomic nervous system.

SUMMARY

A neural stimulation system controls the delivery of neural stimulationusing a respiratory signal as a therapy feedback input. The respiratorysignal is used to increase the effectiveness of the neural stimulation,such as vagal nerve stimulation, white decreasing potentially adverseside effects in respiratory functions.

In one embodiment, a neural stimulation system includes a stimulationoutput circuit, a stimulation delivery controller, a respiratory signalinput, a respiratory disorder detector, and a stimulation switch. Thestimulation output circuit delivers a neural stimulation therapy. Thestimulation delivery controller controls the delivery of the neuralstimulation therapy by executing one or more stimulation algorithms. Therespiratory signal input receives a respiratory signal indicative ofrespiratory cycles. The respiratory disorder detector detects arespiratory disorder using the respiratory signal. The stimulationswitch stops executing a stimulation algorithm response to the detectionof the respiratory disorder.

In one embodiment, a method for neural stimulation is provided. Thedelivery of neural stimulation is controlled by executing one or morestimulation algorithms. A respiratory signal indicative of respiratorycycles is received. A respiratory disorder is detected using therespiratory signal. The execution of a stimulation algorithm is stoppedin response to the detection of the respiratory disorder.

In one embodiment, a neural stimulation system includes a stimulationoutput circuit, a respiratory signal input, and a synchronizationmodule. The stimulation output circuit delivers neural stimulationpulses. The respiratory signal input receives a respiratory signalindicative of respiratory cycles and respiratory parameters. Thesynchronization module includes a peak detector and a delay timer. Thepeak detector detects peaks of the respiratory signal. The delay timertimes a delay interval starting with each of the detected peaks of therespiratory signal. The stimulation delivery controller causes thestimulation output circuit to deliver a burst of the neural stimulationpulses when the delay interval expires.

In one embodiment, a method for neural stimulation is provided. Arespiratory signal is received. Peaks of the respiratory signal arereceived. Delay intervals are started with selected peaks of thedetected peaks. A burst of neural stimulation pulses is delivered wheneach of the delay intervals expires.

This Summary is an overview of some of the teachings of the presentapplication and not intended to be an exclusive or exhaustive treatmentof the present subject matter. Further details about the present subjectmatter are found in the detailed description and appended claims. Otheraspects of the invention will be apparent to persons skilled in the artupon reading and understanding the following detailed description andviewing the drawings that form a part thereof. The scope of the presentinvention is defined by the appended claims and their legal equivalents.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate generally, by way of example, variousembodiments discussed in the present document. The drawings are forillustrative purposes only and may not be to scale.

FIG. 1 is an illustration of an embodiment of a neural stimulationsystem and portions of an environment in which the neural stimulationsystem is used.

FIG. 2 is an illustration of a respiratory signal indicative ofrespiratory cycles and respiratory parameters.

FIG. 3 is an illustration of a delivery of neural stimulation pulsessynchronized to respiratory cycles.

FIG. 4 is a block diagram illustrating an embodiment of a respiratorycycle-synchronized neural stimulation system.

FIG. 5 is a block diagram illustrating a specific embodiment of therespiratory cycle-synchronized neural stimulation system of FIG. 4.

FIG. 6 is a flow chart illustrating an embodiment of a method forsynchronizing neural stimulation to respiratory cycles.

FIG. 7 is a block diagram illustrating an embodiment of a respiratorydisorder-responsive neural stimulation system.

FIG. 8 is a block diagram illustrating a specific embodiment of therespiratory disorder-responsive neural stimulation system of FIG. 7.

FIG. 9 is a flow chart illustrating an embodiment of a method foradjusting neural stimulation in response to a respiratory disorder.

FIG. 10 is a flow chart illustrating a specific embodiment of the methodfor adjusting neural stimulation in response to a respiratory disorder.

FIG. 11 is a block diagram illustrating an embodiment of a respiratorycycle-synchronized respiratory disorder-responsive neural stimulationsystem.

FIG. 12 is a block diagram illustrating an embodiment of anotherrespiratory disorder-responsive neural stimulation system.

FIG. 13 is a block diagram illustrating a specific embodiment of therespiratory disorder-responsive neural stimulation system of FIG. 12.

FIG. 14 is a flow chart illustrating an embodiment of a method forresponding to a respiratory disorder during neural stimulation.

FIG. 15 is a flow chart illustrating an embodiment of a method forcontrolling a neural stimulation treating a non-respiratory disorder.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings which form a part hereof, and in which is shown byway of illustration specific embodiments in which the invention may bepracticed. These embodiments are described in sufficient detail toenable those skilled in the art to practice the invention, and it is tobe understood that the embodiments may be combined, or that otherembodiments may be utilized and that structural, logical and electricalchanges may be made without departing from the spirit and scope of thepresent invention. References to “an”, “one”, or “various” embodimentsin this disclosure are not necessarily to the same embodiment, and suchreferences contemplate more than one embodiment. The following detaileddescription provides examples, and the scope of the present invention isdefined by the appended claims and their legal equivalents.

The relationship between a respiratory rate and a respiratory cyclelength (also known as breathing interval), as used in this document, isthe relationship between a frequency and its corresponding period. If arespiratory rate is given in breaths per minute, its correspondingrespiratory cycle length in seconds is calculated by dividing 60 by therespiratory rate (where 60 is the number of seconds in a minute). Anyprocess, such as a comparison, using a respiratory rate is to bemodified accordingly when a respiratory cycle length is used instead.For example, if a low respiratory rate is detected when the respiratoryrate falls below a threshold rate, an equivalent process is to detectthe low respiratory rate when the respiratory cycle length exceeds acorresponding threshold interval. The appended claims should beconstrued to cover such variations.

This document discusses a neural stimulation system that synchronizesdelivery of neural stimulation to respiratory cycles and/or adjustsdelivery of neural stimulation in response to detection of a respiratorydisorder (disordered breathing) such as apnea, hypopnea, or dyspnea. Inone embodiment, the neural stimulation system delivers neuralstimulation to autonomic nerves such as the vagus nerve of theparasympathetic nervous system. The stimulation of the vagus nerve isreferred to as vagal nerve stimulation or vagal nerve modulation. Vagalnerve stimulation may be applied to treat heart diseases, hypertension,inflammatory disease, epilepsy, diabetes, depression, and otherailments. However, vagal nerve stimulation may also cause undesirableeffects in respiration such as reduced respiratory rate and reducedtidal volume, and worsen the condition of a patient who already suffersfrom a respiratory disorder. Therefore, respiratory disorders such asapnea, hypopnea, and dyspnea have been contraindication for vagal nervestimulation. In one embodiment, the neural stimulation system senses arespiratory signal indicative of respiratory cycles and synchronizes thedelivery of neural stimulation to the respiratory cycles. This providesan inherent negative feedback that reduces the intensity of neuralstimulation when the respiratory rate decreases. In another embodiment,the neural stimulation system detects respiratory disorders such asapnea, hypopnea, and dyspnea. If such a respiratory disorder isdetected, the delivery of neural stimulation is adjusted to reduce theintensity of stimulation, suspend the stimulation, or apply arespiratory therapy using neural stimulation or other means to treat thedetected respiratory disorder. In other embodiments, the neuralstimulation system also delivers neural stimulation to the sympatheticsystem.

While vagal nerve stimulation is discussed as a specific example ofneural stimulation, the present subject matter is applicable to anyneural stimulation that affects respiration. While delivery of “neuralstimulation pulses” to the nervous system is discussed as a specificexample of neural stimulation, the present subject matter is applicableto stimulation of the nervous system using various energy forms andvarious signal morphologies. In one embodiment, the neural stimulationincludes delivery of electrical pulses to the nervous system toartificially elicit action potentials in the nervous system. In otherembodiments, the neural stimulation includes delivery of any form ofenergy that is capable of eliciting or modulating neural activities inthe nervous system, such as electrical, mechanical, thermal, optical,chemical, and biological energies.

FIG. 1 is an illustration of an embodiment of a neural stimulationsystem 100 and portions of an environment in which system 100 is used.System 100 includes implantable medical device 110 that delivers neuralstimulation pulses through leads 106 and 108, an external system 120,and a telemetry link 125 providing for communication between implantablemedical device 110 and external system 120. For illustrative purposesonly, FIG. 1 shows that lead 106 includes an electrode 107 coupled to anerve 102 of the sympathetic nervous system, and lead 108 includes anelectrode 109 coupled a nerve 104 of the parasympathetic nervous system.Nerves 102 and 104 innervate a heart 101. In various embodiments,implantable medical device 110 provides neural stimulation to any one ormore nerves through one or more leads for modulating one or morefunctions of the circulatory system including heart 101. Such leadsinclude implantable neural leads each including at least one electrodefor sensing neural activities and/or delivering neural stimulationpulses. One example of such an electrode includes a cuff electrode forplacement around the vagus nerve.

Implantable medical device 110 delivers the neural stimulation pulsesand includes a respiration-controlled neural stimulation circuit 130.Respiration-controlled neural stimulation circuit 130 controls thedelivery of neural stimulation pulses using indications of respiratorycycles and functions extracted from a respiratory signal. In oneembodiment, respiration-controlled neural stimulation circuit 130detects a predetermined type respiratory fiducial point from eachrespiratory cycle and synchronizes the delivery of neural stimulationpulses to that respiratory fiducial point. In another embodiment,respiration-controlled neural stimulation circuit 130 detectspredetermined type respiratory disorders and suspends or adjusts thedelivery of neural stimulation pulses upon detection of a respiratorydisorder. In one embodiment, implantable medical device 110 is capableof monitoring physiologic signals and/or delivering therapies inaddition to the neural stimulation. Examples of such additionaltherapies include cardiac pacing therapy, cardioversion/defibrillationtherapy, cardiac resynchronization therapy, cardiac remodeling controltherapy, drug therapy, cell therapy, and gene therapy. In variousembodiments, implantable medical device 110 delivers the neuralstimulation in coordination with one or more such additional therapies.

External system 120 provides for control of and communication withimplantable medical device 110 by a physician or other caregiver. In oneembodiment, external system 120 includes a programmer. In anotherembodiment, external system 120 is a patient management system includingan external device communicating with implantable medical device 110 viatelemetry link 125, a remote device in a remote location, and atelecommunication network linking the external device and the remotedevice. The patient management system allows access to implantablemedical device 110 from the remote location, for purposes such asmonitoring patient status and adjusting therapies. In one embodiment,telemetry link 125 is an inductive telemetry link. In an alternativeembodiment, telemetry link 125 is a far-field radio-frequency (RF)telemetry link. Telemetry link 125 provides for data transmission fromimplantable medical device 110 to external system 120. This includes,for example, transmitting real-time physiologic data acquired byimplantable medical device 110, extracting physiologic data acquired byand stored in implantable medical device 1110, extracting patienthistory data such as occurrences of arrhythmias and therapy deliveriesrecorded in implantable medical device 110, and/or extracting dataindicating an operational status of implantable medical device 110(e.g., battery status and lead impedance). Telemetry link 125 alsoprovides for data transmission from external system 120 to implantablemedical device 110. This includes, for example, programming implantablemedical device 110 to acquire physiologic data, programming implantablemedical device 110 to perform at least one self-diagnostic test (such asfor a device operational status), programming implantable medical device110 to deliver one or more therapies and/or to adjust the delivery ofone or more therapies, and/or transmitting externally acquiredphysiologic and/or other patient data for used by implantable medicaldevice 110 to control the one or more therapies.

FIG. 2 is an illustration of a respiratory signal indicative ofrespiratory cycles and respiratory parameters including respiratorycycle length, inspiration period, expiration period, non-breathingperiod, and tidal volume. The inspiration period starts at the onset ofthe inspiration phase of a respiratory cycle, when the amplitude of therespiratory signal rises above an inspiration threshold, and ends at theonset of the expiration phase of the respiratory cycle, when theamplitude of the respiratory cycle peaks. The expiration period startsat the onset of the expiration phase and ends when the amplitude of therespiratory signal falls below an expiration threshold. Thenon-breathing period is the time interval between the end of theexpiration phase and the beginning of the next inspiration phase. Thetidal volume is the peak-to-peak amplitude of the respiratory signal.

The respiratory signal is a physiologic signal indicative of respiratoryactivities. In various embodiments, the respiratory signal includes anyphysiology signal that is modulated by respiration. In one embodiment,the respiratory signal is a transthoracic impedance signal sensed by animplantable impedance sensor. In another embodiment, the respiratorysignal is extracted from a blood pressure signal that is sensed by animplantable pressure sensor and includes a respiratory component. Inanother embodiment, the respiratory signal is sensed by an externalsensor that senses a signal indicative of chest movement or lung volume.

FIG. 3 is an illustration of a delivery of neural stimulation pulsessynchronized to respiratory cycles. In the illustrated embodiment, peaks320 of a respiratory signal 300 are detected as the respiratory fiducialpoints. A delay interval 330 starts upon the detection of each of peaks320. A burst of neural stimulation pulses 310 is delivered to a nervesuch as the vagus nerve when delay interval 330 expires. In variousother embodiments, onset points of the inspiration phases, ending pointsof the expiration phases, or other threshold-crossing points aredetected as the respiratory fiducial points.

FIG. 4 is a block diagram illustrating an embodiment of a respiratorycycle-synchronized neural stimulation system 440. System 440 includes arespiratory sensor 426, a sensor processing circuit 428, andrespiration-controlled neural stimulation circuit 430.

Respiratory sensor 426 senses a physiologic signal indicative of therespiratory cycles and the respiratory parameters. In one embodiment,respiratory sensor 426 includes an implantable sensor incorporated intoimplantable medical device 110. In a specific embodiment, respiratorysensor 426 is an impedance sensor that senses a transthoracic impedancesignal indicative of respiration. In another embodiment, respiratorysensor 426 includes an implantable sensor or a portion thereof. Theimplantable sensor is communicatively coupled to the implantable medicaldevice via one or more leads or via telemetry. In a specific embodiment,respiratory sensor 426 is an implantable pulmonary artery pressure (PAP)sensor or a portion thereof. The implantable PAP sensor communicateswith implantable medical device 100 via RF or ultrasonic telemetry. Anexample of the implantable PAP sensor is discussed in U.S. patentapplication Ser. No. 11/249,624, entitled “METHOD AND APPARATUS FORPULMONARY ARTERY PRESSURE SIGNAL ISOLATION”, filed on Oct. 13, 2005, nowissued as U.S. Pat. No. 7,566,308, assigned to Cardiac Pacemakers, Inc.,which is incorporated by reference herein in its entirety. In anotherembodiment, respiratory sensor 426 includes an external sensor thatsenses the expansion and contraction of the chest or a portion thereof.The external sensor communicates with implantable medical device 100 viaRF or ultrasonic telemetry.

Sensor processing circuit 428 produces the respiratory signal using thephysiologic signal. The respiratory signal is indicative of respiratorycycles and respiratory parameters including one or more of respiratorycycle length, inspiration period, expiration period, non-breathingperiod, tidal volume, and minute ventilation. In one embodiment, sensorprocessing circuit 428 removes unwanted components of the physiologicsignal to isolate the respiratory components of the physiologic signal.One example includes isolating the respiratory components of a PAPsignal, which is discussed in U.S. patent application Ser. No.11/249,624, now issued as U.S. Pat. No. 7,566,308. In one embodiment,sensor processing circuit 428 extracts one or more of the respiratoryparameters. In one embodiment, sensor processing circuit 428 andrespiration-controlled neural stimulation circuit 430 are both housed inimplantable medical device 110. In another embodiment, sensor processingcircuit 428 is part of an implantable or external sensor that includesrespiratory sensor 426.

Respiration-controlled neural stimulation circuit 430 is a specificembodiment of respiration-controlled neural stimulation circuit 130 andincludes a stimulation output circuit 432 and a controller 434.Stimulation output circuit 432 delivers neural stimulation pulses viaelectrodes such as electrodes 107 and 109. Controller 434 includes arespiratory signal input 436, a synchronization module 438, and astimulation delivery controller 446. Respiratory signal input 436receives the respiratory signal indicative of respiratory cycles andrespiratory parameters. Synchronization module 438 synchronizes thedelivery of the neural stimulation pulses to the respiratory cycles andincludes a respiratory fiducial point detector 442 and a delay timer444. Respiratory fiducial point detector 442 detects predetermined-typerespiratory fiducial points in the respiratory signal. Delay timer 444times a delay interval starting with each of the detected respiratoryfiducial points. Stimulation delivery controller 446 causes stimulationoutput circuit 432 to deliver a burst of the neural stimulation pulseswhen the delay interval expires.

FIG. 5 is a block diagram illustrating an embodiment of a respiratorycycle-synchronized neural stimulation system 540, which is a specificembodiment of respiratory cycle-synchronized neural stimulation system440. System 540 includes respiratory sensor 426, sensor processingcircuit 428, and a respiration-controlled neural stimulation circuit530.

Respiration-controlled neural stimulation circuit 530 is a specificembodiment of respiration-controlled neural stimulation circuit 430 andincludes stimulation output circuit 432, a sensing circuit 550, and acontroller 534. Sensing circuit 550 senses one or more neural signalsusing electrodes such as electrodes 107 and 109. Controller 534 includesrespiratory signal input 436, a synchronization module 538, and astimulation delivery controller 546. Synchronization module 538synchronizes the delivery of the neural stimulation pulses to therespiratory cycles. Such synchronization between respiratory cycles andneural stimulation provides a negative feedback to mitigate undesirableeffects such as abnormally long respiratory cycle lengths caused by theneural stimulation. In one embodiment, the synchronization betweenrespiratory cycles and neural stimulation allows the neural stimulationto mimic the natural heart rate modulation by the respiration where theheart rate increases during the inspiration phase and decreases duringthe expiration phase. In a further embodiment, in addition tosynchronizing neural stimulation to respiratory cycles, synchronizationmodule 538 also synchronizes the neural stimulation to cardiac cyclesand/or circadian cycles. Synchronization module 538 includes a peakdetector 542, a delay timer 544, and a delay generator 548. Peakdetector 542 is a specific embodiment of respiratory fiducial pointdetector 442 and detects high or low peaks of the respiratory signal. Inone embodiment, peak detector 542 detects high peaks illustrated in FIG.3 as peaks 320. Delay timer 544 times the delay interval that startswith the detected peaks. In one embodiment, the delay interval isprogrammable between approximately 0 and 5 seconds. In anotherembodiment, delay generator 548 adjusts the delay interval using therespiratory signal. In a specific embodiment, delay generator 548calculates the delay interval as a function of the respiratory cyclelength. Stimulation delivery controller 546 is a specific embodiment ofstimulation delivery controller 446 and controls the delivery of theneural stimulation pulses by executing a stimulation algorithm includinga set of stimulation parameters. In various embodiments, the stimulationparameters include pulse amplitude, pulse width, stimulation frequencyor inter-pulse interval, number of pulses per burst, and stimulationsites. Stimulation delivery controller 546 causes stimulation outputcircuit 432 to deliver a burst of the neural stimulation pulses when thedelay interval expires.

FIG. 6 is a flow chart illustrating an embodiment of a method 600 forsynchronizing neural stimulation to respiratory cycles. In oneembodiment, method 600 is performed by respiration-controlled neuralstimulation circuit 430 or 530.

A respiratory signal is received at 610. The respiratory signal isindicative of respiratory cycles and respiratory parameters. Examples ofthe respiratory parameters include the respiratory cycle length, theinspiration period, the expiration period, the non-breathing interval,the tidal volume, and the minute ventilation. In various embodiments,the respiratory signal is, or is derived from, a physiologic signalindicative of the respiratory cycles and the respiratory parameters.Examples of the physiologic signal include a transthoracic impedancesignal and blood pressure signals such as a PAP signal.

A respiratory fiducial point is detected from the respiratory signal at620. Examples of the respiratory fiducial point include high or lowpeaks of the respiratory signal and threshold-crossing points in therespiratory signal.

A delay interval is started at 630, when the respiratory fiducial pointis detected. In one embodiment, the delay interval is programmablebetween approximately 0 and 5 seconds. In another embodiment, the delayinterval is adjusted using the respiratory signal. In a specificembodiment, the delay interval is calculated as a function of therespiratory cycle length and/or one or more other respiratory parametersextracted from the respiratory signal.

A burst of neural stimulation pulses is delivered when the delayinterval expires at 640. In various embodiments, the delivery of theneural stimulation pulses is controlled by executing a stimulationalgorithm including a set of stimulation parameters such as one or moreof pulse amplitude, pulse width, stimulation frequency or inter-pulseinterval, number of pulses per burst, and stimulation sites.

FIG. 7 is a block diagram illustrating an embodiment of a respiratorydisorder-responsive neural stimulation system 740. System 740 includesrespiratory sensor 426, sensor processing circuit 428, and arespiration-controlled neural stimulation circuit 730.

Respiration-controlled neural stimulation circuit 730 is a specificembodiment of respiration-controlled neural stimulation circuit 130 andincludes stimulation output circuit 432 and a controller 760. Controller760 includes respiratory signal input 436, a respiratory disorderdetector 752, a stimulation adjustment module 754, and a stimulationdelivery controller 756. Respiratory disorder detector 752 detectspredetermined-type respiratory disorders using the respiratory signalreceived by respiratory signal input 436. Stimulation adjustment module754 adjusts the delivery of the neural stimulation pulses in response tothe detection of each of the respiratory disorders. In one embodiment,stimulation adjustment module 754 stops the execution of a stimulationalgorithm in response to the detection of a respiratory disorder.Stimulation delivery controller 756 controls the delivery of the neuralstimulation pulses by executing one or more stimulation algorithms.

FIG. 8 is a block diagram illustrating an embodiment of a respiratorydisorder-responsive neural stimulation system 840, which is a specificembodiment of respiratory disorder-responsive neural stimulation system740. System 840 includes respiratory sensor 426, sensor processingcircuit 428, a physiologic sensor 870, another sensor processing circuit872, and a respiration-controlled neural stimulation circuit 830.

Physiologic sensor 870 senses one or more physiologic signals inaddition to the physiologic signal sensed by respiratory sensor 426 andthe one or more neural signals sensed by sensing circuit 550. In variousembodiments, physiologic sensor 870 senses one or more of cardiacsignals, signals indicative of heart sounds, cardiac and/ortransthoracic impedance signals, and signals indicative of blood oxygenlevel. Sensor processing circuit 872 processes the one or morephysiologic signals sensed by physiologic sensor 870 for use byrespiration-controlled neural stimulation circuit 830 in controlling theneural stimulation. In various embodiments, physiologic sensor 870 orportions of physiologic sensor 870 are included in implantable medicaldevice 110 or communicatively coupled to implantable medical device 110via one or more leads or telemetry. In various embodiments, sensorprocessing circuit 872 or portions sensor processing circuit 872 areincluded in implantable medical device 110 or communicatively coupled toimplantable medical device 110 via one or more leads or telemetry.

Respiration-controlled neural stimulation circuit 830 is a specificembodiment of respiration-controlled neural stimulation circuit 130 andincludes stimulation output circuit 432, sensing circuit 550, and acontroller 860. Controller 860 is a specific embodiment of controller760 and includes respiratory signal input 436, a respiratory disorderdetector 852, a physiologic signal input 876, a physiologic eventdetector 874, a stimulation adjustment module 854, and a stimulationdelivery controller 856.

Respiratory disorder detector 852 detects one or more respiratorydisorders using the respiratory signal. In the illustrated embodiment,respiratory disorder detector 852 includes an apnea detector 862, ahypopnea detector 864, and a dyspnea detector 866. In various otherembodiments, respiratory disorder detector 852 includes any one or moreof apnea detector 862, hypopnea detector 864, and dyspnea detector 866.In various embodiments, respiratory disorder detector 852 also detectsabnormal values of one or more respiratory parameters, such as a lowrespiratory rate when the respiratory rate is below a threshold rate, alow tidal volume when the tidal volume is below a detection thresholdvolume, and a low minute ventilation when the minute ventilation isbelow a detection threshold value.

Apnea is characterized by abnormally long non-breathing periods. Apneadetector 862 detects apnea by comparing the non-breathing period to adetection threshold period. Apnea is detected when the non-breathingperiod exceeds the detection threshold period. Hypopnea is characterizedby abnormally shallow breathing, i.e., low tidal volume. Hypopneadetector 864 detects hypopnea by comparing the tidal volume to adetection threshold volume. Hypopnea is detected when the tidal volumeis below the detection threshold volume. In one embodiment, the tidalvolume is an average tidal volume over a predetermined time interval ora predetermined number of respiratory cycles. Dyspnea is characterizedby rapid shallow breathing, i.e., high respiratory rate-to-tidal volumeratio. Dyspnea detector 866 detects dyspnea by comparing the ratio ofthe respiratory rate to the tidal volume to a detection threshold ratio.Dyspnea is detected when the ratio exceeds the threshold ratio. Invarious embodiments, the threshold period, the detection thresholdvolume, and/or the threshold ratio are empirically established. Anexample of apnea and hypopnea detection using a respiratory signal suchas a transthoracic impedance signal is discussed in U.S. patentapplication Ser. No. 10/309,770, entitled “DETECTION OF DISORDEREDBREATHING,” filed on Dec. 4, 2002, published as US 2004/0111040 A1, nowissued as U.S. Pat. No. 7,252,640, assigned to Cardiac Pacemakers, Inc.,which is incorporated by reference herein in its entirety. An example ofdyspnea detection using a respiratory signal such as a transthoracicimpedance signal is discussed in U.S. patent application Ser. No.11/229,316, entitled “RAPID SHALLOW BREATHING DETECTION FOR USE INCONGESTIVE HEART FAILURE STATUS DETERMINATION,” filed on Sep. 16, 2005,published as US 2007/0073168 A1, now issued as U.S. Pat. No. 7,775,983,assigned to Cardiac Pacemakers, Inc., which is incorporated by referenceherein in its entirety.

Physiologic signal input 876 receives the one or more physiologicsignals sensed by physiologic sensor 870 and processed by sensorprocessing circuit 872. Physiologic event detector 874 detects one ormore physiologic events from the one or more physiologic signals. Invarious embodiments, physiologic event detector 874 detects one or moreof changes in cardiac signal morphology, changes in heart sound waveformmorphology, changes in impedance signal morphology, and changes in bloodoxygen saturation.

Stimulation adjustment module 854 adjusts the delivery of the neuralstimulation pulses in response to at least the detection of arespiratory disorder by respiratory disorder detector 852. In oneembodiment, stimulation adjustment module 854 adjusts the delivery ofthe neural stimulation pulses in response to detection of a respiratorydisorder by respiratory disorder detector 852 and the detection of aphysiologic event by physiologic event detector 874. Stimulationdelivery controller 856 controls the delivery of the neural stimulationpulses by executing one or more stimulation algorithms. Stimulationadjustment module 854 includes a stimulation switch 868. Stimulationswitch 868 stops executing a first stimulation algorithm in response tothe detection of a respiratory disorder such as apnea, hypopnea, ordyspnea. For example, the first stimulation algorithm is executed totreat a cardiac condition by vagal nerve stimulation. If apnea,hypopnea, or dyspnea is detected, the vagal nerve stimulation is to bestopped to avoid the worsening of the condition due to the vagal nervestimulation designed for treating the cardiac condition. In oneembodiment, stimulation switch 868 resumes the execution of the firststimulation algorithm after a predetermined suspension period. Inanother embodiment, stimulation switch 868 resumes the execution of thefirst stimulation algorithm when the respiratory disorder is no longerdetected. In another embodiment, stimulation switch 868 resumes theexecution of the first stimulation algorithm after a predeterminedsuspension period. In another embodiment, stimulation switch 868 resumesthe execution of the first stimulation algorithm in response to astimulation command issued by a user such as a physician using externalsystem 120. In one embodiment, in addition to stopping the execution ofthe first stimulation algorithm, stimulation switch 868 starts executinga second stimulation algorithm in response to the detection of therespiratory disorder. In a specific embodiment, the second stimulationalgorithm provides lower stimulation intensity when compared to thefirst stimulation algorithm. Switching from the first stimulationalgorithm to the second stimulation algorithm lowers the stimulationpulse amplitude, shortens stimulation pulse width, lowers thestimulation frequency, reduces the number of pulses per burst, and/orchanges stimulation sites. In another specific embodiment, the firststimulation algorithm is used to treat a non-respiratory disorder suchas a cardiac disorder, and the second stimulation algorithm is used totreat the detected respiratory disorder, such as apnea, hypopnea, anddyspnea. Switching from the first stimulation algorithm to the secondstimulation algorithm switches the treatment for the non-respiratorydisorder to the treatment for the respiratory disorder. In anotherspecific embodiment, the first stimulation algorithm is used to treatthe non-respiratory disorder, and the second stimulation algorithm isused to treat the detected respiratory disorder in addition to treatingthe non-respiratory disorder. Switching from the first stimulationalgorithm to the second stimulation algorithm switches the treatment forthe non-respiratory disorder to the treatment for both the respiratorydisorder and the non-respiratory disorder.

In one embodiment, the “respiratory disorder” discussed in this documentrefers to a respiratory disorder associated with sleep (i.e., sleepdisordered breathing, such as sleep apnea, sleep hypopnea, or sleepdyspnea). The one or more physiologic signals indicate whether a patientis sleeping. For example, physiologic sensor 870 includes an activitysensor, a posture sensor, and/or one or more other sensors that senses asignal being a factor indicating sleeping. Physiologic event detector874 detects sleeping based on the one or more physiologic signals andproduces a sleeping signal indicating whether the patient is sleeping.In one embodiment, physiologic event detector 874 detects sleeping basedon the one or more physiologic signals and the time of the day.Respiratory disorder detector 852 detects such one or more respiratorydisorders when the sleeping signal is present. Stimulation adjustmentmodule 854 adjusts the delivery of the neural stimulation pulses inresponse to at least one respiratory disorder detected during sleep. Inother embodiments, the “respiratory disorder” discussed in this documentincludes a respiratory disorder that occurs while the patient is awakeor sleep.

In one embodiment, the “respiratory disorder” discussed in this documentrefers to a respiratory disorder induced by neural stimulation. Apatient may have one or more respiratory disorders that are unrelated tothe vagal nerve stimulation. The respiratory disorder induced by neuralstimulation includes a respiratory disorder that is caused or worsenedby the vagal nerve stimulation. In one embodiment, the one or morephysiologic signals sensed by physiologic sensor 870 indicate whether arespiratory disorder is induced by the vagal nerve stimulation. Forexample, because speech may interfere with the detection of the one ormore respiratory disorders, physiologic sensor 870 includes anaccelerometer or microphone to detect a signal indicative of speech.Physiologic event detector 874 detects speech using the signal andproduces a speech signal indicating whether the patient is talking.Respiratory disorder detector 852 detects one or more respiratorydisorders when the speech signal is not present. In another example,respiratory disorder detector 852 detects the one or more respiratorydisorders using the respiratory signal sensed during the vagal nervestimulation and stored baseline respiratory parameters. The baselinerespiratory parameters are produced from the respiratory signal sensedwhile the vagal nerve stimulation is not delivered. Respiratory disorderdetector 852 uses the baseline respiratory parameters to isolate theeffect of the vagal nerve stimulation in the respiratory signal for thedetection of the one or more respiratory disorders. In variousembodiments, respiratory disorder detector 852 detects one or morerespiratory disorders induced by vagal nerve stimulation using therespiratory signal and other signals such as a signal indicative ofwhether the vagal nerve stimulation is being delivered, a signalindicative of time of the day, and one or more physiologic signalsallowing for determination of whether a respiratory disorder is causedor worsened by the vagal nerve stimulation. Stimulation adjustmentmodule 854 adjusts the delivery of the neural stimulation pulses inresponse to at least one respiratory disorder induced by the delivery ofthe neural stimulation pulses.

FIG. 9 is a flow chart illustrating an embodiment of a method 900 foradjusting neural stimulation in response to a respiratory disorder. Inone embodiment, method 900 is performed by respiration-controlled neuralstimulation circuit 730 or 830.

The neural stimulation is controlled by using a plurality of stimulationparameters at 910. The neural stimulation is delivered to treat anon-respiratory disorder. In one embodiment, neural stimulation isdelivered to treat a cardiac condition, such as to treat heart failureor to control cardiac remodeling.

A respiratory signal is received at 920. The respiratory signal isindicative of respiratory cycles and respiratory parameters. Examples ofthe respiratory parameters include the respiratory cycle length, theinspiration period, the expiration period, the non-breathing period, thetidal volume, and the minute ventilation. In various embodiments, therespiratory signal is, or is derived from, a physiologic signalindicative of the respiratory cycles and the respiratory parameters.Examples of the physiologic signal include a transthoracic impedancesignal and blood pressure signals such as a PAP signal.

A respiratory disorder is being detected at 930. Examples of therespiratory disorder include abnormal respiratory parameter values suchas low respiratory rate, low tidal volume, and low minute ventilation,apnea, hypopnea, and dyspnea. Apnea is detected when the non-breathingperiod exceeds a detection threshold period. Hypopnea is detected whenthe tidal volume is below a detection threshold volume. Dyspnea isdetected when the ratio of the respiratory rate to the tidal volumeexceeds a detection threshold ratio.

If the respiratory disorder is detected at 935, the neural stimulationis adjusted by adjusting one or more of the stimulation parameters at940. The neural stimulation is adjusted to terminate or mitigate thedetected respiratory disorder. In one embodiment, the neural stimulationis adjusted to decrease the intensity of the stimulation. In anotherembodiment, the neural stimulation is suspended for a predeterminedperiod of time or until the respiratory disorder is no longer detected.In another embodiment, the neural stimulation is adjusted to treat thedetected respiratory disorder.

FIG. 10 is a flow chart illustrating an embodiment of a method 1000 foradjusting neural stimulation in response to the detection of arespiratory disorder. Method 1000 is a specific embodiment of method900. In one embodiment, method 1000 is performed byrespiration-controlled neural stimulation circuit 730 or 830.

The neural stimulation is controlled by executing a first stimulationalgorithm at 1010. In one embodiment, the first stimulation algorithm isdesigned to treat a cardiac condition, such as heart failure.

A respiratory signal is received at 1020. The respiratory signal isindicative of respiratory cycles and respiratory parameters. Examples ofthe respiratory parameters include the respiratory cycle length, theinspiration period, the expiration period, the non-breathing period, thetidal volume, and the minute ventilation. In various embodiments, therespiratory signal is, or is derived from, a physiologic signalindicative of the respiratory cycles and the respiratory parameters.Examples of the physiologic signal include a transthoracic impedancesignal and blood pressure signals such as PAP signal.

A respiratory disorder is being detected at 1030. Examples of therespiratory disorder include abnormal respiratory parameter values suchas low respiratory rate, low tidal volume, and low minute ventilation,apnea, hypopnea, and dyspnea. Apnea is detected when the non-breathingperiod exceeds a detection threshold period. Hypopnea is detected whenthe tidal volume is below a detection threshold volume. Dyspnea isdetected when the ratio of the respiratory rate to the tidal volumeexceeds a detection threshold ratio.

If the respiratory disorder is detected at 1035, the execution of thefirst stimulation algorithm is stopped at 1040. Whether to execute asecond stimulation algorithm is determined at 1050. If the secondstimulation algorithm is determined to be executed at 1055, the neuralstimulation is controlled by executing the second stimulation algorithmat 1070. In one embodiment, the second stimulation algorithm is selectedto lower the stimulation intensity by the first stimulation algorithm.In another embodiment, the second stimulation algorithm is selected totreat the detected respiratory disorder, such as apnea, hypopnea, ordyspnea.

If the second stimulation algorithm is determined not to be executed at1055, whether to resume the execution of the first stimulation algorithmis determined at 1060. During or after the execution of the secondstimulation algorithm, whether to resume the execution of the firststimulation algorithm is also determined at 1060. If the execution ofthe first stimulation algorithm is resumed at 1065, the neuralstimulation is again controlled by executing a first stimulationalgorithm at 1010. In one embodiment, the execution the firststimulation algorithm is to be resumed after a predetermined suspensionperiod. In another embodiment, the execution the first stimulationalgorithm is to be resumed when the respiratory disorder is no longerdetected. In another embodiment, the execution the first stimulationalgorithm is to be resumed in response to a stimulation command issuedby a user such as a physician.

In one embodiment, in addition to the response to the detection of therespiratory disorder, the delivery of the neural stimulation pulses isadjusted in response to the detection of a physiologic event. Examplesof such a physiologic event include changes in cardiac signalmorphology, changes in heart sound waveform morphology, changes inimpedance signal morphology, and changes in blood oxygen saturation.

FIG. 11 is a block diagram illustrating an embodiment of a respiratorycycle-synchronized respiratory disorder-responsive neural stimulationsystem 1140. System 1140 represents a combination of systems 440 or 540and systems 740 or 840. In the illustrated embodiment, system 1140includes respiratory sensor 426, sensor processing circuit 428, and arespiration-controlled neural stimulation circuit 1130. In variousspecific embodiments, system 1140 may include any combination ofcomponents of systems 440, 540, 740, and 840 as discussed above.

Respiration-controlled neural stimulation circuit 1130 is a specificembodiment of respiration-controlled neural stimulation circuit 130 andincludes stimulation output circuit 432 and a controller 1180.Controller 1180 includes respiratory signal input 436, respiratorydisorder detector 752, stimulation adjustment module 754,synchronization module 438, and stimulation delivery controller 1182.Stimulation delivery controller 1182 controls the delivery of the neuralstimulation pulses from stimulation output circuit 432 by synchronizingthe delivery to the respiratory cycles, as controlled by synchronizationmodule 438, and by responding to the detection of each respiratorydisorder, as controlled by stimulation adjustment module 754.

FIG. 12 is a block diagram illustrating an embodiment of a respiratorydisorder-responsive neural stimulation system 1240. System 1240 includesrespiratory sensor 426, sensor processing circuit 428, and arespiration-controlled neural stimulation circuit 1230.

Respiration-controlled neural stimulation circuit 1230 is anotherspecific embodiment of respiration-controlled neural stimulation circuit130 and includes a therapy output device 1284 and a controller 1286.Therapy output device 1284 delivers one or more therapies including aneural stimulation therapy treating a non-respiratory disorder.Controller 1286 includes respiratory signal input 436, respiratorydisorder detector 752, a therapy adjustment module 1288, and a therapydelivery controller 1290. Therapy adjustment module 1288 adjustsdelivery of the one or more therapies in response to the detection of arespiratory disorder by respiratory disorder detector 752. Therapydelivery controller 1290 controls the delivery of the one or moretherapies using parameters set and adjusted by therapy adjustment module1288.

In one embodiment, system 1240 provides for one or more neuralstimulation therapies that include at least one neural stimulationtherapy treating a non-respiratory disorder. When the respiratorydisorder is detected, system 1240 starts a neural stimulation therapytreating the detected respiratory disorder and/or adjusts the neuralstimulation therapy treating the non-respiratory disorder. When arespiratory disorder such as apnea is detected, the neural stimulationtherapy is suspended or adjusted for a lower intensity, or a separateneural stimulation therapy is delivered to treat the detectedrespiratory disorder. In another embodiment, system 1240 provides theneural stimulation therapy treating the non-respiratory disorder andanother therapy treating the detected respiratory disorder. When therespiratory disorder is detected, system 1240 starts the other therapytreating the detected respiratory disorder and/or adjusts the neuralstimulation therapy treating the non-respiratory disorder.

FIG. 13 is a block diagram illustrating an embodiment of a respiratorydisorder-responsive neural stimulation system 1340, which is a specificembodiment of respiratory disorder-responsive neural stimulation system1240. System 1340 includes respiratory sensor 426, sensor processingcircuit 428, and a respiration-controlled neural stimulation circuit1330.

Respiration-controlled neural stimulation circuit 1330 is a specificembodiment of respiration-controlled neural stimulation circuit 1230 andincludes a therapy output device 1384 and a controller 1386. Therapyoutput device 1384 includes a non-respiratory stimulation output circuit1332 and a respiratory therapy output device 1396. Non-respiratorystimulation output circuit 1332 delivers the neural stimulation therapythrough electrodes or transducer(s) to treat a non-respiratory disorder,such as a cardiac disorder. Respiratory therapy output device 1396delivers a respiratory therapy that treats the detected respiratorydisorder. In one embodiment, respiratory therapy output device 1396delivers another neural stimulation therapy through electrodes ortransducer(s) to treat the respiratory disorder, such as by stimulatingdifferent nerves or nerve branches. Examples of treating respiratorydisorders using neural stimulation are discussed in U.S. patentapplication Ser. No. 11/151,122, entitled “SYSTEM FOR NEURAL CONTROL OFRESPIRATION,” filed on Jun. 13, 2005, published as US 20060282131, nowissued as U.S. Pat. No. 8,036,750, and U.S. patent application Ser. No.11/320,500, entitled “NEURAL STIMULATOR TO TREAT SLEEP DISORDEREDBREATHING,” filed on Dec. 28, 2005, now issued as U.S. Pat. No.7,672,728, both assigned to Cardiac Pacemakers, Inc., which areincorporated by reference herein in their entirety. In anotherembodiment, respiratory therapy output device 1396 delivers a therapytreating the respiratory disorder that is other than a neuralstimulation therapy. Examples of such therapies treating the respiratorydisorder include cardiac pacing therapies and an external pressuretherapy. An example of treating respiratory disorders using cardiacpacing is discussed in U.S. patent application Ser. No. 10/798,794,entitled “RATE REGULARIZATION OF CARDIAC PACING FOR DISORDERED BREATHINGTHERAPY,” filed on Mar. 11, 2004, now issued as U.S. Pat. No. 7,336,996,assigned to Cardiac Pacemakers, Inc., which is incorporated by referenceherein in its entirety. An example of treating respiratory disordersusing an external pressure therapy, delivered by a continuous positiveairway pressure (CPAP) device controlled by an implantable medicaldevice, is discussed in U.S. patent application Ser. No. 10/930,979,entitled “coordinated use of respiratory and cardiac therapies for sleepdisordered breathing,” filed on Aug. 31, 2004, now issued as U.S. Pat.No. 7,591,265, assigned to Cardiac Pacemakers, Inc., which isincorporated by reference herein in its entirety.

Controller 1386 includes respiratory signal input 436, respiratorydisorder detector 752, a therapy adjustment module 1388, and a therapydelivery controller 1390. Therapy adjustment module 1388 includes anon-respiratory stimulation adjustment module 1354 and a respiratorytherapy adjustment module 1392 to provide for a coordinated response toeach detection of the respiratory disorder by respiratory disorderdetector 752. In one embodiment, in response to the detection of therespiratory disorder, respiratory therapy adjustment module 1392 startsthe delivery of the respiratory therapy that treats the detectedrespiratory disorder. If the respiratory disorder is terminated ormitigated to a tolerable degree in response to the delivery of therespiratory therapy, non-respiratory stimulation adjustment module 1354does not adjust the neural stimulation therapy treating thenon-respiratory disorder. If the respiratory disorder is not terminatedor mitigated to the tolerable degree in response to the delivery of therespiratory therapy, non-respiratory stimulation adjustment module 1354stops the delivery, or reduces the intensity, of the stimulation therapytreating the non-respiratory disorder. In another embodiment, inresponse to the detection of the respiratory disorder, respiratorytherapy adjustment module 1392 starts the delivery of the respiratorytherapy that treats the detected respiratory disorder, andnon-respiratory stimulation adjustment module 1354 stops the delivery,or reduces the intensity, of the stimulation therapy treating thenon-respiratory disorder. Non-respiratory stimulation adjustment module1354 resumes the normal delivery of the stimulation therapy treating thenon-respirator disorder after a predetermined time interval or when therespiratory disorder is no longer detected by respiratory disorderdetector 752, such as by restoring stimulation parameters to those usedprior to the detection of the respiratory disorder. Therapy deliverycontroller 1390 includes a non-respiratory stimulation deliverycontroller 1356 and a respiratory therapy delivery controller 1394.Non-respiratory stimulation delivery controller 1356 controls thedelivery of the stimulation therapy treating the non-respiratorydisorder using stimulation parameters set and adjusted bynon-respiratory stimulation adjustment module 1354. Respiratory therapydelivery controller 1394 controls the delivery of the respiratorytherapy treating the detected respiratory disorder using therapy (neuralor cardiac stimulation, or other types of therapy) parameters set andadjusted by respiratory therapy adjustment module 1392.

In one embodiment, system 1340 allows for a neural stimulation therapyto be applied to a patient who is otherwise contraindicated for thatneural stimulation therapy. For example, vagal nerve stimulation isknown to improve hemodynamic performance and/or controlling ventricularremodeling in heart failure patients. However, a substantial percentageof heart failure patients also suffer apnea, and the vagal nervestimulation may worsen that abnormal respiratory condition. System 1340potentially allows application of vagal nerve stimulation to these heartfailure patients while monitoring or treating the apnea, therebyremoving apnea as a contraindication for vagal nerve stimulation. Inthis embodiment, respiratory disorder detector 752 includes at leastapnea detector 862. In a specific embodiment, in addition to respondingto the detection of apnea, non-respiratory stimulation adjustment module1354 provides feedback control of the vagal nerve stimulation improvinghemodynamics and/or controlling ventricular remodeling using anon-respiratory physiological parameter as an input. The feedbackcontrol functions to maintain the non-respiratory physiologicalparameter within a target range. For example, non-respiratorystimulation adjustment module 1354 receives cardiac parameters such asthe patient's heart rate or heart rate variability and adjusts theintensity of the vagal nerve stimulation to maintain the heart rate orheart rate variability within a target range.

FIG. 14 is a flow chart illustrating an embodiment of a method 1400 foradjusting neural stimulation in response to the detection of arespiratory disorder. The neural stimulation is a therapy for treating anon-respiratory disorder, such as heart failure. In one embodiment,method 1400 is performed by respiration-controlled neural stimulationcircuit 1230 or 1330.

The neural stimulation is controlled by using stimulation parameters at1410. In one embodiment, the stimulation parameters are selected fortreating a cardiac condition, such as to improve hemodynamic performanceor control ventricular remodeling in a heart failure patient. A specificembodiment of step 1410 is discussed below, with reference to FIG. 15.

A respiratory signal is received at 1420. The respiratory signal isindicative of respiratory cycles and respiratory parameters. Examples ofthe respiratory parameters include the respiratory cycle length, theinspiration period, the expiration period, the non-breathing period, thetidal volume, and the minute ventilation. In various embodiments, therespiratory signal is, or is derived from, a physiologic signalindicative of the respiratory cycles and the respiratory parameters.Examples of the physiologic signal include a transthoracic impedancesignal and blood pressure signals such as a PAP signal.

A respiratory disorder is being detected at 1430. Examples of therespiratory disorder include abnormal respiratory parameter values suchas low respiratory rate, low tidal volume, and low minute ventilation,apnea, hypopnea, and dyspnea. In one embodiment, apnea is detected whilethe neural stimulation is applied to the heart failure patient.

If the respiratory disorder is detected at 1435, a respiratory therapyis delivered at 1440, to treat the detected respiratory disorder. In oneembodiment, the respiratory therapy includes another neural stimulationtherapy which uses stimulation parameters selected to treat the detectedrespiratory disorder. In another embodiment, the respiratory therapyincludes one or more therapies other than neural stimulation.

Whether the detected respiratory disorder is mitigated is determined at1450 by comparing a respiratory parameter to a mitigation threshold. Thedetected respiratory disorder is considered “mitigated” when its degreeis reduced to a tolerable degree at which the detected respiratorydisorder is considered not to be harmful to the patient. In variousembodiments, the respiratory disorder is detected by comparing therespiratory parameter to a detection threshold, and whether the detectedrespiratory disorder is mitigated is determined by comparing therespiratory parameter to the mitigation threshold. In one embodiment,the detection threshold and the mitigation threshold are equal. Inanother embodiment, the detection threshold and the mitigation thresholdare substantially different. For example, apnea is detected when thenon-breathing period exceeds a detection threshold period, and isdetermined to be mitigated when the non-breathing period falls below amitigation threshold period. Hypopnea is detected when the tidal volumeis below a detection threshold volume, and is determined to be mitigatedwhen the tidal volume rises above a mitigation threshold volume. Dyspneais detected when the ratio of the respiratory rate to the tidal volumeexceeds a detection threshold ratio, and is determined to be mitigatedwhen that ratio falls below a mitigation threshold ratio.

If it is determined that the detected respiratory disorder has beenmitigated at 1455, the neural stimulation is continued to be controlledat 1410 without adjusting the stimulation parameters selected to treatthe non-respiratory disorder. If it is determined that the detectedrespiratory disorder has not been mitigated at 1455, the stimulationparameters are adjusted at 1460 for lowering the intensity, or stoppingthe delivery, of the neural stimulation for treating the non-respiratorydisorder.

FIG. 15 is a flow chart illustrating an embodiment of a method 1500 forcontrolling the neural stimulation treating the non-respiratorydisorder. Method 1500 represents a specific embodiment of step 1410 ofmethod 1400. In one embodiment, method 1500 is performed bynon-respiratory stimulation adjustment module 1354.

Method 1500 provides for feedback control of the neural stimulationtreating the non-respiratory disorder. The neural stimulation isdelivered at 1510, using the stimulation parameters selected to treatthe non-respiratory disorder. A non-respiratory response to the neuralstimulation is monitored at 1520. If the non-respiratory response iswithin a target range at 1525, the neural stimulation is continued to bedelivered at 1510, without adjusting the stimulation parameters. If thenon-respiratory response is not within a target range at 1525, thestimulation parameters are adjusted at 1530, and the neural stimulationis continued to be delivered at 1510 using the adjusted stimulationparameters. In one embodiment, the non-respiratory response is measuredby a non-respiratory physiological parameter. For example, for a neuralstimulation therapy treating a cardiac disorder, method 1500 is appliedto maintain one or more of cardiac parameters such as heart rate, heartrate variability, and blood pressure each within its target range.

With step 1410 performed using method 1500, method 1400 allows theneural stimulation to be adjusted for both treatment of thenon-respiratory disorder while limiting potential harm associated withan adverse side effect of the neural stimulation. For example, for aheart failure patient, method 1400 allows the neural stimulation to beadjusted for maintaining a parameter such as heart rate, heart ratevariability, or blood pressure within its predetermined target rangewithout causing or worsening a sustained apnea.

It is to be understood that the above detailed description is intendedto be illustrative, and not restrictive. Other embodiments will beapparent to those of skill in the art upon reading and understanding theabove description. The scope of the invention should, therefore, bedetermined with reference to the appended claims, along with the fullscope of equivalents to which such claims are entitled.

What is claimed is:
 1. A neural stimulation system, comprising: astimulation output circuit configured to deliver neural stimulationpulses; a respiratory signal input configured to receive a respiratorysignal indicative of respiratory cycles and respiratory parameters; asynchronization module coupled to the stimulation output circuit and therespiratory signal input, the synchronization module including: a peakdetector coupled to the respiratory signal input, the peak detectorconfigured to detect peaks of the respiratory signal; and a delay timercoupled to the peak detector, the delay timer configured to time a delayinterval starting with each of the detected peaks of the respiratorysignal; and a stimulation delivery controller coupled to the delay timerand the stimulation output circuit, the stimulation delivery controllerconfigured to cause the stimulation output circuit to deliver a burst ofthe neural stimulation pulses when the delay interval expires.
 2. Thesystem of claim 1, wherein the synchronization module comprises a delaygenerator configured to adjust the delay interval using the respiratorysignal.
 3. The system of claim 2, wherein the delay generator isconfigured to calculate the delay interval as a function of one or moreparameters of the respiratory parameters.
 4. The system of claim 1,further comprising: an implantable medical device including thestimulation output circuit, the respiratory signal input, thesynchronization module, and the stimulation delivery controller; animplantable respiratory sensor configured to sense a physiologic signal;and a sensor processing circuit configured to produce the respiratorysignal using the physiologic signal.
 5. The system of claim 4, whereinthe implantable respiratory sensor comprises an implantable impedancesensor configured to sense a transthoracic impedance.
 6. The system ofclaim 4, wherein the implantable respiratory sensor comprises animplantable pulmonary artery pressure (PAP) sensor.
 7. The system ofclaim 1, further comprising: a respiratory disorder detector coupled tothe respiratory signal input, the respiratory disorder detectorconfigured to detect a respiratory disorder using the respiratorysignal; and a stimulation switch coupled to the respiratory disorderdetector and the stimulation delivery controller, the stimulation switchconfigured to adjust the delivery of the neural stimulation pulses inresponse to the detection of the respiratory disorder.
 8. The system ofclaim 7, wherein the respiratory disorder detector is configured todetect abnormal values in one or more parameters of the respiratoryparameters.
 9. The system of claim 7, wherein the respiratory disorderdetector is configured to detect a respiratory disorder induced by thedelivery of the neural stimulation pulses.
 10. The system of claim 7,wherein the stimulation switch is configured to stop executing a firststimulation algorithm and start executing a second stimulation algorithmin response to the detection of the respiratory disorder.
 11. A methodfor neural stimulation, the method comprising: receiving a respiratorysignal indicative of respiratory parameters; detecting peaks of therespiratory signal; starting delay intervals with selected peaks of thedetected peaks; and delivering a burst of neural stimulation pulses ofthe neural stimulation when each of the delay intervals expires.
 12. Themethod of claim 11, further comprising programming the delay interval toa time interval between approximately 0 and 5 seconds.
 13. The method ofclaim 11, further comprising adjusting the delay interval using therespiratory signal.
 14. The method of claim 13, wherein adjusting thedelay interval using the respiratory signal comprises: detecting arespiratory rate from the respiratory signal; and calculating the delayinterval as a function of the respiratory rate.
 15. The method of claim11, wherein receiving the respiratory signal comprises receiving atransthoracic impedance signal.
 16. The method of claim 11, whereinreceiving the respiratory signal comprises receiving a pulmonary arterypressure (PAP) signal.
 17. The method of claim 11, further comprising:detecting a respiratory disorder using the respiratory signal; andadjusting delivery of the neural stimulation in response to thedetection of the respiratory disorder.
 18. The method of claim 17,wherein detecting the respiratory disorder detector comprises detectingabnormal values in one or more parameters of the respiratory parameters.19. The method of claim 17, wherein detecting the respiratory disorderdetector comprises detecting a respiratory disorder induced by thedelivery of the neural stimulation.
 20. The method of claim 17, whereinadjusting delivery of the neural stimulation in response to thedetection of the respiratory disorder comprises stopping execution of afirst stimulation algorithm and starting execution of a secondstimulation algorithm in response to the detection of the respiratorydisorder.